Proteomic analysis of citrullinated targets regulated by the p53-PADI4 pathway

• Project/Area Number: 25710009
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Tumor biology
• Research Institution: The University of Tokyo
• Principal Investigator: Tanikawa Chizu 東京大学, 医科学研究所, 助教 (30422421)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥25,480,000 (Direct Cost: ¥19,600,000、Indirect Cost: ¥5,880,000); Fiscal Year 2015: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000); Fiscal Year 2014: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000); Fiscal Year 2013: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
• Keywords: p53 / シトルリン化 / PADI4

Outline of Final Research Achievements

Although recent proteome analyses have provided a comprehensive overview of various posttranscriptional modifications, the functions associated with protein citrullination remain unclear. Thus, we performed a proteomic screen and identified more than 100 PADI4 substrates associated with RNA processing and translation. Citrullination of RBMX inhibited the interaction with other hnRNP family members. RNA sequence analyses revealed that the splicing patterns of more than 300 genes were disrupted in bone marrow derived from Padi4-/- mice. Citrullination at the RGG motifs was elevated in a number of cancer tissues, and an antibody against citrullinated RGG motifs was observed in 17.5% of serum samples from patients with HCV-induced HCC. Our findings revealed that PADI4-mediated citrullination is associated with RNA processing and tumor immunogenicity and suggest that PADI4 activation has potential therapeutic implications for neurodegenerative disease treatment and cancer immunotherapy.

Research Products

• [Journal Article] Cystatin C as a p53‐inducible apoptotic mediator which regulates Cathepsin L activity (2016)
  • Author(s): Jinichi Mori, Chizu Tanikawa, Yuki Funauchi, Paulisally Hau Yi Lo, Yusuke Nakamura, Koichi Matsuda
  • Journal Title: Cancer science Volume: 107 Issue: 3 Pages: 298-306
  • DOI: 10.1111/cas.12881
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Regulation of myo-inositol biosynthesis by p53-ISYNA1 pathway (2016)
  • Author(s): Tomoyuki Koguchi, Chizu Tanikawa, Jinichi Mori, Yoshiyuki Kojima, Koichi Matsuda
  • Journal Title: International Journal of Oncology Volume: 印刷中 Issue: 6 Pages: 2415-24
  • DOI: 10.3892/ijo.2016.3456
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Regulation of iron homeostasis by the p53-ISCU pathway (2015)
  • Author(s): Yuki Funauchi, Chizu Tanikawa, Paulisally Hau Yi Lo, Jinichi Mori, Yataro Daigo, Atsushi Takano, Yohei Miyagi, Atsushi Okawa, Yusuke Nakamura, Koichi Matsuda
  • Journal Title: Scientific reports Volume: 5 Issue: 1 Pages: 16497-16497
  • DOI: 10.1038/srep16497
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Genome-wide association study identified SNP on 15q24 associated with bladder cancer risk in Japanese population. (2015)
  • Author(s): Matsuda K, Takahashi A, Middlebrooks CD, Obara W, Nasu Y, Inoue K, Tamura K, Yamasaki I, Naya Y, Tanikawa C, Cui R, Figueroa JD, Silverman DT, Rothman N, Namiki M, Tomita Y, Nishiyama H, Kohri K, Deguchi T, Nakagawa M, Yokoyama M, Miki T, Kumon H, Fujioka T, Prokunina-Olsson L, Kubo M, Nakamura Y, Shuin T.
  • Journal Title: Hum Mol Genet. Volume: 24 Issue: 4 Pages: 1177-1184
  • DOI: 10.1093/hmg/ddu512
  • Peer Reviewed
• [Journal Article] Identification of novel epigenetically inactivated gene PAMR1 in breast carcinoma. (2015)
  • Author(s): Lo PH, Tanikawa C, Katagiri T, Nakamura Y, Matsuda K.
  • Journal Title: Oncol Rep Volume: 33 Issue: 1 Pages: 267-273
  • DOI: 10.3892/or.2014.3581
  • Peer Reviewed
• [Journal Article] Late Cornified Envelope Group I, a novel target of p53, regulates PRMT5 activity. (2014)
  • Author(s): Deng Z, Matsuda K, Tanikawa C, Lin J, Furukawa Y, Hamamoto R, Nakamura Y.
  • Journal Title: Neoplasia Volume: 16 Issue: 8 Pages: 656-664
  • DOI: 10.1016/j.neo.2014.07.008
  • Peer Reviewed
• [Journal Article] Downregulation of the tumor suppressor HSPB7, involved in the p53 pathway, in renal cell carcinoma by hypermethylation. (2014)
  • Author(s): Lin J, Deng Z, Tanikawa C, Shuin T, Miki T, Matsuda K, Nakamura Y.
  • Journal Title: Int J Oncol Volume: 44 Issue: 5 Pages: 1490-1498
  • DOI: 10.3892/ijo.2014.2314
  • Peer Reviewed
• [Journal Article] Impact of PSCA variation on gastric ulcer susceptibility. (2013)
  • Author(s): C. Tanikawa, K. Matsuo, M. Kubo, A. Takahashi, H. Ito, H. Tanaka, Y. Yatabe, K. Yamao, N. Kamatani, K. Tajima, Y. Nakamura, K. Matsuda
  • Journal Title: Plos one Volume: 8 Issue: 5 Pages: e63698-e63698
  • DOI: 10.1371/journal.pone.0063698
  • Peer Reviewed
• [Journal Article] Genome wide association study of age at menarche in the Japanese population (2013)
  • Author(s): Tanikawa C, Okada Y, Takahashi A, Oda K, et al
  • Journal Title: PLoS One Volume: 8 Issue: 5 Pages: e63821-e63821
  • DOI: 10.1371/journal.pone.0063821
  • Peer Reviewed
• [Journal Article] Identification of a Functional Variant in the MICA Promoter Which Regulates MICA Expression and Increases HCV-Related Hepatocellular Carcinoma Risk. (2013)
  • Author(s): Lo PH, Urabe Y, Kumar V, Tanikawa C, Koike K, Kato N, Miki D, Chayama K, Kubo M, Nakamura Y, Matsuda K.
  • Journal Title: PLoS One. Volume: 8 Issue: 4 Pages: e61279-e61279
  • DOI: 10.1371/journal.pone.0061279
  • Peer Reviewed
• [Presentation] p53による転写制御の組織網羅的解析 (2015)
  • Author(s): 谷川千津、張、井元、山口、宮野、中川英刀、中村祐輔、松田浩一
  • Organizer: 日本癌学会学術集会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] Regulation of RNA processing by PADI4 pathway (2015)
  • Author(s): Chizu Tanikawa, Koji Ueda, Yusuke Nakamura, Koichi Matsuda.
  • Organizer: AACR Annual Meeting
  • Place of Presentation: Philadelphia, Pennsylvania, USA
  • Year and Date: 2015-04-18
  • Int'l Joint Research
• [Presentation] Regulation of RNA processing by p53-PADI4 pathway (2014)
  • Author(s): 谷川千津、植田幸嗣、中川英刀、中村祐輔、松田浩一
  • Organizer: 日本癌学会学術集会
  • Place of Presentation: パシフィコ横浜、神奈川県横浜市
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Proteomic analysis of citrullinated targets regulated by the p53-PADI4 pathway (2014)
  • Author(s): Chizu Tanikawa, Koji Ueda, Hidewaki Nakagawa, Yusuke Nakamura, Koichi Matsuda.
  • Organizer: American Association for Cancer Research
  • Place of Presentation: San Diego, California, USA
  • Year and Date: 2014-04-05 – 2014-04-09
• [Presentation] Proteomic analysis of citrullinated targets regulated by the p53-PADI4 pathway (2013)
  • Author(s): 谷川千津、植田幸嗣、中川英刀、中村祐輔、松田浩一
  • Organizer: 日本癌学会学術集会
  • Place of Presentation: 横浜
• [Presentation] A genome-wide association study identifies two susceptibility loci for duodenal ulcer in the Japanese population (2013)
  • Author(s): Chizu Tanikawa, Koichi Matsuda, Yusuke Nakamura
  • Organizer: American Association for Cancer Research
  • Place of Presentation: Washington, DC, USA